A series of 2-substituted aminoindene hydrochlorides were synthesized in our laboratories and tested for pharmacological activity. The 2-n-propyl and 2-n-butyl aminoindenes proved to be potent intracellular antagonists of calcium in studies involving excitation-contraction coupling in a variety of smooth muscle preparations from several species and in studies involving stimulus-secretion coupling in the bovine adrenal medulla. In addition to having proven value as pharmacological tools in studying the molecular mechanisms of muscle contraction and of glandular secretion, these compounds may have potentially useful antiarrhythmic properties. The aim of this project is threeford: (1) To investigate the potential antiarrhythmic properties of the 2-substituted aminoindenes in both in vivo and in vitro designs. The in vivo studies will utilize digoxin-poisoned dogs, aconitine-poisoned dogs, DDT-poisoned dogs, and calcium-poisoned rats. Cardiovascular parameters to be monitored will include atrial and ventricular rhythms, systolic and end-diastolic blood pressure, force of myocardial contraction, and dp/dt values. In vitro studies will include electrically stimulated atrial and ventricular strips from dog and guinea pig hearts, electrically stimulated rabbit hearts in presence of acetylcholine and low potassium, and measurement of calcium-dependent action potentials in dog cardiac Purkinje fibers. (2) Establishment of a complete toxicological profile for the 2-substituted aminoindenes. (3) Synthesis and pharmacological investigation of chemical analogs of the 2-substituted aminoindenes currently under study.